The unfolded protein response (UPR) events triggered by the accumulation of unfolded protein in endoplasmic reticulum (ER) activate the three UPR signaling pathways mediated by IRE1, ATF6 and PERK. Spliced XBP1 mRNA induced by activated IRE1 is translated to the protein, a potent transcription factor that induces BiP expression. XBP1 is also induced by activated ATF6. It is thus thought to be an important marker reflecting both IRE1 and ATF6 signaling in response to ER stress. For quantitative measurement of XBP1 gene expression, it is important to distinguish between the spliced and non-spliced form of XBP1 mRNA. We have developed a new method to detect the spliced XBP1 mRNA by means of real-time PCR and we compared the result with measurements of the expression of the ER stress inducible gene BiP. A good correlation was found between spliced XBP1 expression and BiP expression. Thus, our method may be useful for simple and quantitative evaluation of ER stress.

SummaryAge-related changes in haematology and serum chemistry values were examined in male and female Weiser-Maples guineapigs (Cavia porcellus). Haematological changes that significantly (Po0.01) correlated with ageing were increased white blood cell and neutrophil counts in both sexes, decreased lymphocyte counts in both sexes, decreased reticulocyte and platelet counts in males, and decreased basophil counts in females. For serum chemistry, increases in total protein, triglycerides, blood urea nitrogen and creatinine were seen in both sexes, along with increases in total cholesterol in males and sodium in females. Decreased alkaline phosphatase in both sexes and decreased chloride in males were significantly (Po0.01) associated with age. These age-related changes are compared with the published literature.

Abstract. Although it has been shown that auricular chondritis in rats is caused by the use of metal identification ear tags, the pathogenesis remains unclear. Based on the hypothesis that the auricular chondritis is caused by metal ions released from metal identification ear tags, we investigated the pathogenesis in male C57BL/6 mice tagged with metal identification ear tags. Twenty-six weeks after the attachment of the ear tags, visible increases in the thickness of the auricle were observed, and the concentrations of copper and iron in the tagged ears were significantly increased (P , .05) in the tagged ears compared with the untagged ears. There was up-regulation of metallothionein (MT)-I and MT-II mRNA in the tagged ears, and this was confirmed by immunohistologic staining of the destroyed cartilage. Histopathologically, there were observed severe chondritis with extensive granulomatous inflammation, newly formed cartilage nodules, and osseous metaplasia accompanied by cellular infiltrates, such as CD4 T lymphocyte, macrophages, neutrophils, and mast cells, and expression of Th1 cytokines, such as interferon-gamma, tumor necrosis factor-alpha, and interleukin-2 in the tagged ear. Based on these results, we concluded that the release of copper and iron ions from the metal ear tags played a major role in the onset of auricular chondritis. Subsequent cellular interactions, such as CD4 T cells, macrophages, fibroblasts, and mast cells, mediated by cytokines, such as tumor necrosis factoralpha and interferon-gamma, caused an autoimmune response that may have led to the progression of auricular chondritis as an autoimmune disease.

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SummaryGross and histopathological features of auricular chondritis in young Crj:CD(SD)IGS rats were examined. Although the rats were identi ed with metallic ear tags on the right pinnae, auricular chondritis was also observed on the contralateral (left) ear in some animals. Histopathologically, the lesions were characterized by granulomatous in ammation with destruction of the normal cartilaginous plate, formation of new cartilaginous nodules and osseous metaplasia. Proliferative cell nuclear antigen (PCNA) positive cells were present predominantly in chondrocytes found in the centre of the newly-formed cartilaginous nodules. The results suggest that the newly-formed cartilaginous nodules were due to interstitial proliferation of chondrocytes.